The Chromosomal basis of Inheritance

– It’s where the genes are….

The Chromosomal Theory of Inheritance

Genes have specific loci on chromosomes

Chromosomes undergo segregation and independent assortment

Chromosomal Linkage Morgan Drosophilia melanogaster

XX (female) vs. XY (male) Sex-linkage: genes located on a

sex chromosome Linked genes: genes located on

the same chromosome that tend to be inherited together

Genetic recombination

Crossing over of linked genes- Now they DO assort independently of each other!

Genetic mapsThe further apart 2 genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency.

Linkage mapsGenetic map based on

recombination frequenciesAnimate!

Human sex-linkage SRY gene: gene on Y chromosome that triggers the development of testes Fathers= pass X-linked alleles to all daughters only (but not to sons) Mothers= pass X-linked alleles to both sons & daughters Sex-Linked Disorders: Color-blindness; Duchene muscular dystrophy (MD); hemophilia

X-inactivation: 2nd X chromosome in females condenses into a Barr body (e.g., tortoiseshell gene gene in cats)

Chromosomal Alterations Non-disjunction: members of a pair

of homologous chromosomes do not separate properly during meiosis I or sister chromatids fail to separate during meiosis II.

Aneuploidy: abnormal number of a certain chromosome. Examples:– Monosomy X ~ Turner Syndrome

• (only viable human monosomy)

– Trisomy 21~ Down Syndrome– Trisomy 13 ~ Patau Syndrome– Trisomy 18 ~Edward’s Syndrome

Polyploidy: more than 2 complete sets of chromosomes.– Comes from non-disjunction of all

chromosomes– Common in Plant Evolution.

Alterations in Chromosome Structure Can result from non-reciprocal crossovers or weak area of chromosomes. Deletion: removal of a chromosomal segment Duplication: repeats a chromosomal segment (a fragment may join a homolog)

Inversion: segment reversal in a chromosome (reattaches in reverse) Translocation: movement of a chromosomal segment to another

Various effects of Chromosomal Alterations:

-Homozygous deletions are usually lethal

-Duplications & translocations usually deleted

-Some reciprocal translocations can alter phenotype because of

“POSITION EFFECT”:

-The influence on a gene’s expression because of its location among neighboring genes.

Genomic imprinting

Identical alleles may have different effects on offspring, depending on whether they arrive in the zygote via the ovum or via the sperm.

“Something” happens to the gene after they arrive to form the zygote

May involve degrees of methylization (CH3 groups)

Example:Fragile X syndrome: higher prevalence of disorder and in males

http://medgen.genetics.utah.edu/photographs/pages/fragile_x.htm

Another example of

GENOMIC IMPRINTINGPrader-Willi / Angelman Syndrome-

Both disorders are caused by a deletion on Chromosome 15 but:

If the altered chromosome came from Dad:Prader-Willi- Mentally handicapped, short, obesehttp://medgen.genetics.utah.edu/photographs/pages/praderwilli.htm

If the altered chromosome came from Mom:Angelman’s Syndrome- motor/mental symptoms, jerky, uncontrolled laughterhttp://medgen.genetics.utah.edu/photographs/pages/angelmann.htm

Most (but not all) Disorders are recessively Inherited.

Defective alleles code for either a malfunctioning protein….or no protein at all.

Heterozygotes can be phenotypically normal if one of the normal copies is all that is needed.

They are, of course, carriers.

Most people with recessive disorders are born to “normal” parents. (carriers)

Probability is ¼ that the mating of 2 carriers will produce a homozygous recessive. …and 2/3 that (s)he will be a carrier.

Consanguinity: condition that results from shared ancestry Results in more homozygous recessives. (Stearns County Syndrome)

REMEMBER!- not all disorders are recessivesome are “late-acting” & occur after sexual maturity.

Example- Huntington’s Disease

Some other Genetic disorders:

Cri-du-Chat: A specific deletion in Chromosome 5mentally handicapped, distorted face, cry that sounds like a cat

Patau Syndrome: Trisomy 13Severely mentally handicapped, cleft lip

http://medgen.genetics.utah.edu/photographs/pages/trisomy_13.htm

Edward’s Syndrome: Trisomy 18Low ears,deformed fingers, heart problems

http://medgen.genetics.utah.edu/photographs/pages/trisomy_18.htm

Chronic Myologenous Leukemia- Portion of Chromosome 22 translocates with portion of chromosome 15